LDL受体基因敲除(LDLR-/-)小鼠
动脉粥样硬化模型高脂肪高胆固醇模型饲料
High-Fat High-Cholesterol Diet of Atherosclerosis for LDL receptor-deficient（LDLR-KO）Mice

【原理】

LDLR基因感敲除(LDLR-/-)小鼠动脉粥样硬化的发生和发展对饲料胆固醇和脂肪含量与类型都比较敏感，因此，高脂肪高胆固醇饲料(HFHC diet)广泛用于动脉粥样硬化模型的造模和相关研究。

当前最常采用的Hayek的西方饮食模型饲料（Western-type diet），属于高脂、高糖、高胆固醇模型饲料，其主要参数如下：

高饱和脂肪（无水奶油），脂肪含量为21%，脂肪热量42%，胆固醇含量为0.2%（添加0.15%）。

该模型饲料在Harlan公司的代码是TD88137，在ResearchDiet公司的代码是D12492，TestDiet公司的代码是58Y1。而在南通特洛菲饲料科技有限公司的饲料代码是TP26300系列，为什么是一个系列的饲料呢？

一是Hayek（88137）模型饲料营养素不是很合理，需要考虑进行优化。

二是Hayek（88137）模型饲料不适合从成年期开始喂养的动物。

关于为什么要优化和优化的重要性的详细说明，请阅读“Hayek（TD88137）西方饮食模型饲料存在的问题和纠正”。

因此，TP26300系列包括了不优化，优化，针对成年期使用三个方案的模型饲料：

TP26300：没有优化；

TP26301：优化了脂肪酸；

TP26303：优化了脂肪酸和微量营养素，适用于未成年期开始喂养；

TP26304：成年期开始喂养，脂肪为无水奶油；

TP26305：成年期开始喂养。脂肪以饱和脂肪为主。

如果你对TP26300系列模型饲料感兴趣，请点击浏览：Hayek（TD88137）西方饮食模型饲料介绍。

LDLR基因敲除小鼠动脉粥样硬化的发生和发展不仅取决于饲料中胆固醇浓度，而且对单不饱和脂肪高度敏感（超过对饱和脂肪的敏感性）。因此，以单不饱和脂肪酸为主的高脂高胆固醇模型饲料可用于复制动脉粥样硬化模型。南通特洛菲饲料科技有限公司的饲料代码分别为TP26370和TP26371，模型饲料的主要参数是：

脂肪以单不包含脂肪酸为主，脂肪18.7%，脂肪热量40%；胆固醇0.2%。

其中，TP26370适用于未成年期开始喂养，TP26371适用于从成年期开始喂养。

TP28500系列是Clinton-Cybulsky高脂高胆固醇模型饲料。

由于Clinton-Cybulsky高脂高胆固醇模型饲料的原先配比存在需要优化之处，因此，南通特洛菲饲料科技有限公司提供了不优化和优化和重新设计三种方案。

以上介绍的是纯化型饲料，价格相对较高。日粮型模型饲料的优点是相对便宜。

TP25700系列模型饲料属于日粮型模型饲料，是以高品质的普通饲料为基础，添加脂肪和胆固醇（高脂高胆固醇饲料），或者添加胆固醇（高胆固醇饲料）。

TP25700系列模型饲料中”系列“二字有两个方面的含义：一是脂肪含量和胆固醇含量不同，从而代码不同（TP257**），二是随着脂肪类型不同而出现系列，例如，TP25704实际上包含了添加不同脂肪类型而成为系列（见下文）。

上表中所列的模型饲料中采用的基础饲料，均为特洛菲饲料科技有限公司的LAD0011饲料，详细情况，请点击浏览网页：LAD0011介绍：脂蛋白代谢及其相关的基因工程大鼠和小鼠的日常喂养饲料。

1.LDLR基因敲除小鼠喂高脂高胆固醇饲料后的表现

LDLR-/-小鼠对高脂高糖饲料敏感，发生肥胖、胰岛素抵抗或糖尿病（血糖升高），而胆固醇加重动脉粥样硬化，因此，有可能是属于糖尿病性动脉粥样硬化和胆固醇所致的动脉粥样硬化的综合体现。

此外，可能伴有非酒精性脂肪肝、胃炎等表现。

2.LDLR基因敲除小鼠喂高脂高胆固醇饲料后的动脉粥样硬化表现

LDLR-/-小鼠动脉粥样硬化从主动脉起始部位（主动脉根部）开始，逐渐向头臂动脉(Brachiocephalic artery)、主动脉、腹主动脉延展。动脉粥样硬化定量时特别要注意头臂动脉的情况。

在普通饲料喂养后也自发地形成高胆固醇血症和动脉粥样硬化，而用上述介绍的模型喂养后，血浆胆固醇水平大幅度升高，动脉粥样硬化发生更早、程度更严重。也就是普通饲料和模型饲料喂养效果的差别在于：出现时间和病变程度的差别。

关于其他有关注意事项，请点击：LDLR-/-小鼠动脉粥样硬化模型的造模和模型饲料要求。

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